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recordings and calcium imaging techniques. Moreover, the represent a fixed cell lineage but rather exist in a plastic
simplified structure of cBOS also allows for more effective cell state. They can acquire or lose stem cell properties with
assessment of cell death and cell identity, greatly enhancing the support of the TME, and this plasticity is central to the
the controllability and reproducibility of experiments. 76 growth, heterogeneity, and therapeutic challenges of GBM
tumors.
3.3. Practical applications of organoids in TBI
TBI is a disruption or lesion of brain function or tissue 4.1.1. Tumor stem cells
caused by an external force, with secondary injuries evolving Within the TME, the interactions of GSCs with various
over a long period and involving complex metabolic, surrounding cells play a crucial role in maintaining and
inflammatory, and degenerative changes. 62,77 Despite promoting their stem-like phenotype. For instance, GSCs
progress in TBI research, key questions remain unresolved, form a complex network of interactions with the neurogenic
limiting comprehensive understanding and therapeutic niche of the subventricular zone, vascular endothelial cells,
development. Organoid models offer a novel approach to particularly those in hypoxic regions, and other components
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address these challenges. The main issues in TBI research of the TME. Moreover, immune cells, especially tumor-
include unclear mechanisms driving neuronal degeneration associated macrophages, influence the behavior of GSCs
following 3D mechanical injury, limited understanding of through their interactions. These interactions are not only
gene expression changes and epigenetic modifications post- vital for maintaining the stem-like phenotype of GSCs
injury, insufficient research on multi-organ interactions, but also play a significant role in the aggressiveness and
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particularly between the CNS and other organ systems, heterogeneity of the tumor. More importantly, the interplay
and lack of effective large-scale screening methods for between GSCs and normal tissue is bidirectional. GSCs
identifying optimal TBI treatments. 79,80 cBOS cultured shape the TME through their interactions with normal
at the air-liquid interface enable the study of cellular tissue, and the TME, in turn, provides a sanctuary for the
functions and dysfunctions using calcium biosensors and survival and expansion of GSCs. This interplay is not only
electrophysiological recordings (Figure 2A). High-intensity crucial in the progression of GBM but may also be one of
focused ultrasound platforms recreate pathological the key reasons for therapy resistance. Thus, the complex
changes in TBI, such as neuronal death and tau protein interplay mechanisms between GSCs and the TME are
phosphorylation, revealing key gene expression changes considered potential targets for the treatment of GBM.
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(Figure 2B). Cellular transplantation using iPSCs and BOs 4.1.2. Tumor vasculature
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promotes neurogenesis, 83,84 mature synaptic connections
and neural networks, and reduces inflammation, showing GBM is characterized by its highly angiogenic nature, which
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potential for neural circuit reconstruction and functional not only supplies the tumor with oxygen and nutrients but
recovery (Figure 2C). Co-culture experiments with “brain also creates a protective microenvironment that supports
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and lung” organoids 87-89 highlight the brain–lung axis, tumor growth and survival. GSCs play a pivotal role in this
revealing systemic effects of TBI. The current research is process by releasing chemokines and angiogenic factors
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limited in capturing multi-organ interactions, emphasizing that actively promote tumor angiogenesis. This process
the need for more sophisticated in vitro models to simulate relies not only on the expansion of local endothelial cells
real physiological conditions in TBI patients. It is worthy but may also involve the recruitment of bone marrow-
to note that existing TBI treatments focus on symptom derived endothelial progenitor cells or other stem cells to
relief and palliative care, with full recovery remaining a form perivascular niches, further strengthening the tumor’s
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significant challenge. vascular network.
4. Organoids in brain tumor The differentiation of GSCs is closely associated with
the formation of perivascular niches, indicating that
4.1. Structure and microenvironment of brain GSCs play a role not only in maintaining tumor stem cell
tumors characteristics but may also be directly involved in the
Despite some advancements through extensive molecular process of vascular formation. Studies have shown that
analysis, GBM remains one of the most aggressive and tumor-derived endothelial cells may arise through the
therapeutically challenging malignant brain tumors. In transdifferentiation of GBM cells, although the specific
recent years, the TME has been recognized as a key player molecular mechanisms of this transdifferentiation are not
in the progression of GBM and is increasingly becoming a yet fully understood. Regardless, these angiogenic processes
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potential therapeutic target. The concept of glioblastoma provide the tumor with a sanctuary that allows it to evade
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stem cells (GSCs), in particular, has provided a new immune surveillance and develop resistance to therapy.
perspective for understanding the complex physiological The presence of the BBB is one of the main reasons for
and pathological mechanisms of GBM. GSCs do not the chemoresistance of GBM. At present, researchers are
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Volume 1 Issue 1 (2025) 6 doi: 10.36922/or.8261